There are many situations in medicine where a wound does not heal properly, such as from compromised wound healing that delays or prevents resolution of a wound. There are further wound healing events, however, that can limit resulting function or cosmesis. Exemplary undesired results include hyperplastic responses that produce extensive scarring, keloids, or wound contracture that compromises function and mobility.
Hypertrophic scars occur when the body overproduces collagen, which causes the scar to be raised above the surrounding skin. Hypertrophic scars often take the form of a red raised lump on the skin and usually occur within four to eight weeks following wound infection or wound closure with excess tension and/or other traumatic skin injuries. Keloid formation in particular is a very challenging wound healing problem. Keloids are defined as benign fibrous (fibroblastic or myofibroblastic) proliferations resulting in soft tissue tumors. The benign hyper-proliferative growth of dense fibrous tissue in keloids develops from an abnormal healing response to a cutaneous injury and is dissimilar to normal wound healing and scarring, including hypertrophic scarring. These differences manifest in cellular processes, collagen production and deposition, continued growth beyond the boundaries of the original wound, and a high recurrence rate after excision. Unlike normal scars or hypertrophic scars, keloids contain fibroblasts that overproduce type I procollagen, VEGF, TGFβ1/β2, PDGF-α receptors, and have reduced growth factor requirements, with either lower rates of apoptosis or a down-regulation of apoptotic genes (Robles, et al., Clinics in Dermatology, 2007). These aberrant fibroblast processes have demonstrated increased production of collagen and extracellular matrix in vitro and in vivo. X-ray diffraction examination of normal, hypertrophic, and keloid scars demonstrates that rather than the collagen fibrils running parallel to the scar line (normal scar) or slightly aligned to the scar line (hypertrophic scars), the collagen fibrils of keloid scars present no specific orientation of the collagen at all (Koonin eta al., S. A. Medical Journal 1964). Additionally, this collagen has been termed “keloid collagen” since the deposition pattern, mixture of collagen types (greater abundance of type III later replaced by type I), and overabundance are unlike other tissue or scar types (Cheng et al. African Journal of Biotechnology 2011). Finally, unlike normal scars or hypertrophic scars, the propensities for recurrence in keloid scars have been reported at 45-100%, and keloids are resistant to known treatments used for scars or hypertrophic scars (Robles, et al., Clinics in Dermatology 2007).
Compositions to promote wound healing have been described with the use of collagen, the main structural protein of the body. In particular, compositions of collagen combined with a glycosaminoglycan, the structural polysaccharides of the body, have also been described to promote wound healing or act as tissue templates for wound repair. For example, U.S. Pat. No. 4,837,024 describes promoting wound healing by contacting a surface of a wound with a suspension of particles of collagen and a glycosaminoglycan. U.S. Pat. No. 4,280,954 describes a composite material containing collagen and a mucopolysaccharide (glycosaminoglycan) that is useful as a degradable surgical prosthesis such as a synthetic skin Compositions using denatured collagen have also been described in wound healing compositions with polysaccharides. U.S. Pat. No. 6,261,587 and U.S. Pat. No. 6,713,079 describe compositions of gelatin and dextran or heparin to be used to stimulate vascularization and promote wound healing. There still remains a need for methods and compositions useful in wound treatment, particularly in addressing keloids and hypertrophic dermal healing.